The present invention relates to a series of new hexahydronaphthalene derivatives related to the class of compounds known as "ML-236B", which have the ability to inhibit the synthesis of cholesterol, and which can thus be used for the treatment and prophylaxis of hypercholesterolemia and of various cardiac disorders. The invention also provides methods and compositions using these compounds as well as processes for their preparation.
Excessive levels of cholesterol in the body have been implicated in many life-threatening disorders and there is, therefore, a need for drugs which have the effect of reducing blood cholesterol levels. One method by which a drug may achieve this is to inhibit the biosynthesis of cholesterol.
A number of compounds which may be generally described as 7-[substituted 1,2,3,5,6,7,8,8a-octahydro-1-naphthyl]-3,5-dihydroxyheptanoates is known, and such compounds are disclosed, inter alia, in European Patent Publication No. 314 435, which also describes in greater detail than herein the development and forerunners of these types of compound. However, the closest compounds to those of the present invention are believed to be the compounds disclosed in United Kingdom Patent Specification No. 2 077 264 and Japanese Pantent Application Kokai No. Sho. 59-175450, which compounds may be represented by the formulae (A) and (B), respectively: ##STR2##
Further hexahydronaphthalene derivatives in this class of prior art compounds are disclosed in a co-pending U.S. patent application, provisionally given the Ser. No. 08/174,661, filed on 28th Dec. 1993.
These prior art compounds, like the compounds of the present invention, have the ability to inhibit the biosynthesis of cholesterol, and can thus be used for the treatment and prophylaxis of the various diseases caused by hypercholesterolemia, such as atherosclerosis and various cardiac disorders.